PROJECT SUMMARY (See instructions); The Radiation Research and Translational Biology, (RRTB) program goal is to improve combination radiation therapies by 1) designing and testing new molecular targets identified by mechanistic studies, and 2) addressing tumor resistance to therapy and bypass of immune surveillance, and 3) designing, assessing and improving technologies that diagnose, stage, and deliver therapies for cancer patients. Program members address these goals with multidisciplinary efforts in biochemistry, immunology, drug design, preclinical models, and clinical experience, to accelerate translation from bench to bedside. The Program has been strengthened by integration of members from the former Program in Cancer Immunology. The current RRTB program, comprised of 34 basic, translational and clinical investigators from eleven departments, thus combines basic and clinical research strengths to conduct bench to bedside research and can reverse translate clinical data to inform further translational innovations. This work is supported by 36 peer-reviewed grants totaling direct funds of $13.2 million ($5.3 million from NCI). The total number of publications generated by Program members from 2007 to 2012 is 543 of which 11% are Intra-programmmatic and 22% are Inter-programmatic, with 4.6% being both. The specific research themes ofthe RRTB Program are: (1) Improve RT therapies by defining and characterizing molecular targets for ionizing radiation and for combined therapies, vaccine development and BMT (2) Immune tolerance and strategies for immune surveillance. (3) Tumor resistance: Microenvironment, hypoxia and angiogenesis. (4) Protecting normal tissues: normal tissue injury/genotoxic stress. (5) Clinical translation of diagnostic and therapeutic innovations, and (6) Improving clinical practice: Biomedical/Bioinformatics and Comparitive Effectiveness Research (CER). This program will continually generate new collaborations, intra- and interprogrammatically, and fresh research directions with other research programs in the cancer center.